October 14 2025
NRG Oncology is currently accruing to the active ComboMATCH EAY191-N5 clinical study in the gynecologic cancer space. EAY191-N5 is part of the National Cancer Institute (NCI) National Clinical Trials Network (NCTN) patient screening trial, ComboMATCH, aimed at directing cancer treatment based on genetic testing across multiple disease sites. The objective of the ComboMATCH studies is to determine if treatment based on genetic testing helps improve outcomes for patients with locally advanced or advanced solid tumors.
Specifically, EAY191-N5 is testing the combination of the drugs neratinib and palbociclib in patients with recurrent or persistent HER2-positive gynecologic cancers. Typically, patients who have HER2-positive gynecologic cancer are treated with neratinib alone. The primary objective of EAY191-N5 is to determine if adding the palbociclib improves progression-free survival for this patient population. Palbociclib, a CDK4 and CDK6 inhibitor, is usually used for treatment of patients with HER2-negative breast cancer.
“This study is intended to assess efficacy of anti-HER2 targeted therapy in a novel combination approach compared to monotherapy not only in anti-HER2 naive but also in anti-HER2 resistant settings to assess if adding CDK4/6 inhibition can improve efficacy or reverse resistance respectively as noted in preclinical studies,” stated Haider Mahdi, MD, MPH, of Magee Women’s Hospital and Principal Investigator of the EAY191-N5 study.
Patients who are enrolled onto this study will be stratified by prior any anti-HER2 therapy then randomly assigned to receive either neratinib alone or neratinib with palbociclib.
In addition to the primary objective, this study also includes several secondary aims, including evaluation of objective response rate, clinical benefit rate, overall survival, grade 3 and 4 toxicities, and collection of tissue for the ComboMATCH Registration Protocol. Further exploratory aims include investigation of the role and trajectory of ctDNA-HER2 status, activation and assessment of specific pathways, and the measuring of HER2 and other protein expressions throughout.